Anxiety-related Behavior In Rats Research Articles

Effect of repeated restraint stress and incisional injury on depression-and anxiety-related behaviour in rats and associated alterations in endocannabinoid levels

Effect of repeated restraint stress and incisional injury on depression-and anxiety-related behaviour in rats and associated alterations in endocannabinoid levels

Influence of enriched environment on anxiety-related behavior in evidence and mechanisms

Anxiety disorders are one of the most prevalent mental disorders that are in a great demand of developing new treatments. Both genetic and environmental factors play essential roles in the pathophysiology of anxiety disorders. Increasing evidence implicates environmental enrichment that shapes neural plasticity exerts beneficial effects on anxiety-related behavior in animal models. Here, we summarize the effects of enriched environment on anxiety-related behavior in rats and mice, highlight the potential mechanisms underlying the beneficial effects of environmental enrichment on emotionality at cellular/molecular level, and discuss the potential directions for further research.

English

The study aims to show the possible anxiolytic and antidepressant-like properties of an oral lavender’s flower aqueous extract (LAE) in chronic mild stress (CMS) model of rats. Test and control rats received LAE (200 or 400 mg/ kg) and distilled water respectively. Tests of Sucrose preference (SP), elevated plus maze (EPM), and open field (OFT) were used to evaluate rats’ behavioral changes.  The percentage of SP in the CMS group was 2.6 times less than that of the unstressed group (p<0.05). However, administration of LAE (200 and 400 mg / kg) increased SP of CMS rats by 2.0 and 3.01 times respectively in comparison to those of the stressed animals. EPM analysis revealed that 5-week CMS exposure significantly reduced the number of entries in open arm (0.8 times) as compared to unstressed rats (6.6 times). LAE (200 and 400 mg / kg) reversed CMS by increasing both the total time spent (1.73 and 1.23% respectively) and the number of entries in open arm (5 and 5.7 times respectively) compared to those related to unstressed group (p< 0.05). CMS decreased the number of entries and time spent in the central zone of OFT. Administration of LAE (200 and 400 mg/ kg) to stressed rats enhanced the total distance traveled respectively by 3.30 and 2.65% than the control rats. Taken together, oral lavender aqueous extracts showed ameliorating effects on the depression and anxiety-related behaviors in rats. Key words: Depression, lavender, chronic mild stress, anxiety, aqueous extract.

The impact of chronic daily nicotine exposure and its overnight withdrawal on the structure of anxiety-related behaviors in rats: Role of the lateral habenula

Tobacco smoking is a serious health problem worldwide and a leading cause of mortality. Nicotine, the addictive component of tobacco, affects a range of emotional responses, including anxiety-related behaviors. Although perceived by smokers to be anxiolytic, evidence suggests that smoking increases anxiety and that mood fluctuates with nicotine intake. Thus, nicotine addiction may depend on easing the psychobiological distress caused by its abuse. The lateral habenula (LHb) has been implicated as a neural substrate for acute nicotine-induced anxiety, but its role in anxiety-like behaviors associated with chronic nicotine exposure has not been explored. Here, we assessed the effect of chronic nicotine exposure and its subsequent overnight withdrawal on anxiety-like behavior using both quantitative and multivariate T-pattern analysis in rats tested using the hole-board apparatus. Additionally, we explored the role of the LHb by comparing the behavioral effects of short-term nicotine withdrawal in chronically treated LHb-lesioned rats. Quantitative analysis revealed increased anxiety-like behavior in chronically treated overnight nicotine-deprived rats, as manifested in reduced general and focused exploratory behaviors, which was eased in animals that received nicotine. Quantitative analysis failed to reveal a role of the LHb in overnight nicotine deprivation-induced anxiety. Conversely, T-pattern analysis of behavioral outcomes revealed that chronic nicotine-treated rats still show anxiety-like behavior following nicotine challenge. Moreover, it demonstrated that the LHb lesion induced a stronger anxiolytic-like response to the acute challenge of nicotine in chronically nicotine-exposed animals, implicating the LHb in the anxiogenic effect of chronic nicotine exposure. These data further highlight the LHb as a promising target for smoking cessation therapies and support the importance of T-pattern analysis for behavioral analysis.

Effects of 2.1 GHz Electromagnetic Radiation on Locomotor Activity, Recognition Memory, and Anxiety-Related Behavior in Rats

The effects of short-term (2 h per day for 7 days) exposures to different doses of 2.1 GHz radiofrequency electromagnetic radiation (RF-EMR) on cognition and behavior of rats were examined. The animals were divided into three equal groups, sham-exposed group 1 and two RF groups irradiated with different doses, groups 2 and 3, respectively. To assess locomotor activity, recognition memory, and anxiety-related behavior, the open field (OF), novel object recognition (NOR), and marble burying (MB) tests were used, respectively. Overall results showed that both 45 and 65 V/m doses of 2.1 GHz RF-EMR did not lead to significant modifications of locomotor activity in the OF test. At the same time, higher doses (65 V/m) significantly (about two times) decreased the exploration time and number of touches for a novel object in the NOR test. In the MB test, both RF-EMR doses led to significant dose-dependent decreases in the number of buried marbles, which was indicative of lower levels of anxiety. Further studies are needed, regarding this particular type and level of radiation, for the development of methods to provide protection of the brain from harmful effects of RF-EMR exposure.

Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats

Acetylcholine is implicated in mood disorders including depression and anxiety. Increased cholinergic tone in humans and rodents produces pro-depressive and anxiogenic-like effects. Cholinergic receptors in the ventral tegmental area (VTA) are known to mediate these responses in male rats, as measured by the sucrose preference test (SPT), elevated plus maze (EPM), and the forced swim test (FST). However, these effects have not been examined in females, and the VTA muscarinic receptor subtype(s) mediating the pro-depressive and anxiogenic-like behavioral effects of increased cholinergic tone are unknown. We first examined the behavioral effects of increased VTA cholinergic tone in male and female rats, and then determined whether VTA muscarinic M5 receptors were mediating these effects. VTA infusion of the acetylcholinesterase inhibitor physostigmine (0.5 μg, 1 μg and 2 μg/side) in males and females produced anhedonic-like, anxiogenic, pro-depressive-like responses on the SPT, EPM, and FST. In females, VTA administration of the muscarinic M5 selective negative allosteric modulator VU6000181 (0.68 ng, 2.3 ng, 6.8 ng/side for a 3 μM, 10 μM, 30 μM/side infusion) did not alter SPT, EPM nor FST behavior. However, in males intra-VTA infusion of VU6000181 alone reduced time spent immobile on the FST. Furthermore, co-infusion of VU6000181 with physostigmine, in male and female rats, attenuated the pro-depressive and anxiogenic-like behavioral responses induced by VTA physostigmine alone, in the SPT, EPM, and FST. Together, these data reveal a critical role of VTA M5 receptors in mediating the anhedonic, anxiogenic, and depressive-like behavioral effects of increased cholinergic tone in the VTA.

4-Nonylphenol and 4-tert-octylphenol induce anxiety-related behaviors through alternation of 5-HT receptors and transporters in the prefrontal cortex

Environmental endocrine disruptors 4-nonylphenol (NP) and 4-tert-octylphenol (OP) may cast huge harm to human health. We used a rat model to observe the influence of NP or/and OP exposure on anxiety-related behaviors and the underlying mechanisms. Eighty male Sprague-Dawley (SD) rats were randomly divided into 10 groups: control group (corn oil), NP groups [30, 90, 270 mg/kg], OP groups [40, 120, 360 mg/kg] and NO groups [(mixed with the corresponding NP, OP alone exposed low, medium and high dose according to the natural environment exists NP:OP = 4:1]. The rats were orally administered every other day for 30 days. The neurobehaviors of rats were evaluated by open-field test (OFT) and elevated plus-maze test (EPM), and the concentrations of 5-HT, monoamine oxidase (MAOA), serotonin transporter (SERT), vesicular monoamine transporter 2 (VAMT2), 5-hydroxytryptamine 1A (5-HT1A), 5-hydroxytryptamine 2A (5-HT2A)，and 5-hydroxytryptamine 2C (5-HT2C) in the rat prefrontal cortex were analyzed by ELISA. OFT and EPM tests showed that NP or/and OP exposure induced anxiety-related behaviors in rats. 5-HT levels were significantly increased compared with the control group. The levels of MAOA, SERT, VAMT2, 5-HT1A, 5-HT2A, and 5-HT2C in the prefrontal cortex reduced in different degrees by high-doses NP or/and OP exposure. In summary, NP or/and OP exposure might cause anxiety-related behaviors in rats through regulating neurotransmitter 5-HT levels by altering the expression of 5-HT decomposition enzyme MAOA, transporters SERT and VMAT2, and 5-HT receptors 5-HT1A, 5-HT2A, and 5-HT2C.

Effects of chronic nicotine on the temporal structure of anxiety-related behavior in rats tested in hole-board

The present study aimed to assess the behavioral effects of chronic treatments of different doses of nicotine by using both quantitative and multivariate T-pattern analysis (TPA), which can reveal hidden behavioral structures, in Sprague-Dawley rats tested in the hole-board apparatus. To this purpose, nicotine ditartrate was administered at the doses of 0.1, 0.5 and 1 mg/kg i.p., three times per day, for 14 consecutive days. As to quantitative evaluations, we observed significant reductions in the mean durations and mean frequencies of walking, climbing, immobile-sniffing and rearing in comparison to control. A significant reduction of edge-sniff and head-dip mean frequencies was also detected for all the doses tested. TPA revealed an increase in the number and the mean length of different T-patterns induced by the three doses of nicotine. On the other hand, a significant reduction of the mean occurrences of T-patterns was revealed. Overall, our results obtained by using both quantitative and T-pattern analyses indicate that chronic nicotine induces an anxiety condition characterized by a behavioral re-organization orbiting around the two main components of hole exploration, that is, head-dip and edge-sniff. A better understanding of the link between nicotine and anxiety might help to find new therapies for smoking cessation.

Short-term sleep fragmentation enhances anxiety-related behavior: The role of hormonal alterations.

IntroductionThe neuroendocrine background of acute sleep fragmentation in obstructive sleep apnea and sleep fragmentation involvement in psychiatric comorbidities, common in these patients, are still largely unknown. The aim of this study was to determine the effects of short-term experimental sleep fragmentation on anxiety -like behavior and hormonal status in rats.MethodsMale rats were adapted to treadmill (ON and OFF mode with belt speed set on 0.02m/s and 0.00m/s) and randomized to: 1) treadmill control (TC, only OFF mode); 2) motion, activity control (AC, 10min ON and 30min OFF mode) and 3) sleep fragmentation (SF, 30s ON and 90s OFF mode) group. Six hours later, the animals were tested in the open field, elevated plus maze and light/dark test (n = 8/group). Testosterone, estradiol, progesterone and corticosterone were determined in separate animal cohort immediately upon sleep fragmentation (n = 6/group).ResultsSF rats showed decreased rearings number, decreased time spent in the central area and increased thigmotaxic index compared to TC and AC rats in the open field test. Similarly, increased anxiety upon sleep fragmentation was observed in the elevated plus maze and the light/dark test. Significantly lower testosterone, estradiol and progesterone levels were determined in SF in comparison to AC and TC groups, while there was no significant difference in the levels of corticosterone.ConclusionShort term sleep fragmentation enhances anxiety-related behavior in rats, which could be partly mediated by the observed hormonal changes presented in the current study in form of testosterone, estradiol and progesterone depletion.

Differential effects of Combined Stress during adolescence and adulthood on Anxiety-related Behaviors in Rats

Differential effects of Combined Stress during adolescence and adulthood on Anxiety-related Behaviors in Rats

Influence of various intensities of 528Hz sound-wave in production of testosterone in rat's brain and analysis of behavioral changes.

Testosterone is a nuclear androgen receptor ligand that controls multiple pathways in brain. In addition to the active biosynthesis of steroids in classic steroidogenic organs such as gonads, adrenals and placenta, testosterone also produced in astrocyte cells of brain. Testosterone and its level must be regulated in brain; because, it directly and indirectly affects memory and several key behavioral characteristics. The significance of sound waves on key enzymes that regulate levels of testosterone in brain has not been investigated. The aim of our study was to examine physical stress of such as sound on induction behavioral changes in animal models. According to the current study, sound waves with 528Hz frequency in 100dB intensity induce testosterone production in brain by enhancing StAR and SF-1 and reducing P450 aromatase gene expression. Frequency of 528Hz also reduces total concentration of reactive oxidative species in brain tissue. Prolonged exposure to this sound wave showed reduction of anxiety related behaviors in rats. The results reveal that reduced anxiety is related to increased concentration of testosterone in brain. This study may lead to ascertain a possible therapy in which sounds may be utilized to reduce anxiety in individual.

Carbenoxolone Reverses the Amyloid Beta 1-42 Oligomer-Induced Oxidative Damage and Anxiety-Related Behavior in Rats.

The characteristic feature of Alzheimer's disease (AD) is the deposition of amyloid beta inside the brain mainly consisting of Aβ 40 and 42 aggregates. Soluble aggregates of Aβ 42 are reported to be more toxic and exert their neurotoxicity by the induction of oxidative damage and cognitive deficits such as anxiety-like behavior. These alterations emerge due to the induction of gap junction communication through increased activity and expression of connexins such as connexin43 (Cx43) leading to the release of small neurotoxic molecules. In the present study, single intracerebroventricular (icv) injection of Aβ 42 oligomers (10μl/rat) was used to induce oxidative damage and anxiety-related behavior in rats. Carbenoxolone (Cbx), a gap junction blocker, was tested (20mg/kg body weight, i.p., for 6weeks) against these alterations. Cbx supplementation reversed the Aβ 42 oligomer-induced alterations in the antioxidant defense system. The levels ROS, lipid peroxidation, and protein carbonyls were normalized with Cbx co-treatment leading to the decreased DNA fragmentation and pyknosis in different regions of the rat brain. Cbx induced the anxiolytic behavior and ameliorated the cognitive decline in rats post Aβ 42 oligomer injection. The increased expression of Cx43 post Aβ 42 oligomer injection was also reduced with Cbx supplementation, which might have inhibited the release of small neurotoxic molecules. Our results showed that Cbx prevents the Aβ 42 oligomer-induced oxidative damage and anxiety-like behavior partly by blocking the gap junction communication, which suggests that the therapeutic potential of Cbx may be explored in the progression of AD.

Sex-dependent modification by chronic caffeine of acute methamphetamine effects on anxiety-related behavior in rats

For fourteen days, male and female PVG/c hooded rats were provided continuously with either pure drinking water, or water containing caffeine in a quantity approximating a daily dose of 31.1 mg/kg. Then at intervals of 3 days, they were administered 1, 2 mg/kg methamphetamine (MA) or saline before being tested for anxiety-related behavior in a zero maze or a light/dark box, or their short-term spatial memory was assessed in a Y maze following introduction of a novel brightness change in one of the arms. Each rat experienced each type of apparatus with the same acute MA or saline treatment while still exposed to chronic caffeine or pure drinking water. While chronic caffeine on its own did not affect any behavioral measure, acute MA was anxiolytic for male rats suggested by increased entries and occupancy of zero-maze enclosed areas, and decreased emergence latencies and increased entries into the light/dark-box light compartment. Females were less affected than males by MA in both types of apparatus unless they also consumed caffeine. For male rats, choices of the Y-maze novel arm were affected by neither caffeine nor MA, but for females provided with unadulterated water, such choices were reduced by 1 mg/kg MA but increased for those exposed to caffeine, thereby suggesting either impaired or improved memory respectively. However, changes in anxiety could also explain these results. Overall, results generated in the three types of apparatus supported potentiation by caffeine of any effects of MA on anxiety for females only.

Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal

For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects.

Adolescent Oral Methylphenidate Treatment Causes Post-administration Increase in Weight Gain and Hyperphagia with no Effect on Anxiety-related Behaviours in Rats

Methylphenidate (MPH) is a widely abused drug that has been shown to be a neural stimulant, amidst concern that it could be neurotoxic. The present study evaluated the changes in body weight, food intake and anxiety-related behaviours following oral administration of MPH to adolescent rats. Thirty- two (32) male adolescent wistar rats were divided into two groups and orally administered either saline vehicle or MPH from post-natal day (PD) 30 twice daily for 14 days. Body weight and food intake were monitored during administration and post-administration periods till PD 70. Anxiety-related activities were assessed using open-field (OF) and elevated plus maze (EPM) task on PD 45 and 70. Animals that received oral MPH administration showed significant decrease in weight gain but average food intake was not altered significantly during administration period. On the other hand, following discontinuation of MPH administration, treated rats recorded a significant increase in weight gain and average food intake. There was no significant treatment effect on central locomotion and time spent in open arms, which are indices of anxiety in the OF and EPM respectively. The study suggests that cessation of oral MPH treatments may induce a post-administration hyperphagia and a resultant effect of increased rate of weight gain. Also, the findings did not show anxiety modulatory actions of MPH following oral administration.

Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats

Background/AimsDai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior.MethodsRats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10, 20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze.ResultsColorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicle-treated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distention-induced ACTH release, corticosterone levels, or anxiety-related behavior in rats.ConclusionsOur results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress.

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light-dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

Ventral tegmental area muscarinic receptors modulate depression and anxiety-related behaviors in rats

Cholinergic and dopaminergic mechanisms within the mesolimbic dopamine system are suggested to play a role in the manifestation of depression and anxiety-related disorders. However, despite the fact that cholinergic mechanisms in the ventral tegmental area (VTA) highly regulate dopamine activity, the role of VTA cholinergic mechanisms in depression-related behaviors is relatively unknown. Here we sought to determine whether enhancing cholinergic tone in the VTA would alter depression and anxiety-related behavior in the forced swim test (FST), elevated plus maze (EPM) and sucrose preference test (SPT). Adult Sprague Dawley male rats received VTA infusion of the acetylcholinesterase inhibitor, physostigmine (0, 1, 2μg/side), immediately prior to the FST, EPM, or SPT. Physostigmine administration increased immobility time in the FST, decreased time spent on open arms in the EPM, and decreased sucrose preference. We also examined whether activation of VTA muscarinic receptors was sufficient to alter behavior in the FST and EPM. Similar to physostigmine, VTA infusion of the muscarinic receptor agonist, pilocarpine (0, 3, 30μg/side), increased immobility time in the FST and decreased time spent on open arms in the EPM. These data suggest that enhanced VTA cholinergic tone promotes pro-depressive and anxiogenic-like effects and demonstrate that specific activation of VTA muscarinic receptors is also sufficient to induce pro-depressive and anxiogenic responses. Together, these findings reveal a novel role of VTA cholinergic, and specifically muscarinic receptor, mechanisms in mediating responses to stress and anxiety.

Food Deprivation, Body Weight Loss and Anxiety-Related Behavior in Rats.

Simple SummaryFood deprivation protocols are frequently used in behavioral studies. However, there is limited evidence as to when food deprivation compromises animal welfare. Regarding the refinement of experiments involving animals, this study investigated the effects of food deprivation on body weight loss and behavior in male and female rats. Sex difference in behavior and motivational state after food deprivation is the main finding of the study. The data highlights the need for tailored pilot experiments to evaluate the impact of food deprivation on animals with regard to the 3Rs principles (replacement, reduction, refinement) in animal science.In behavioral studies, food deprivation protocols are routinely used to initiate or maintain motivational states that are required in a particular test situation. However, there is limited evidence as to when food deprivation compromises animal welfare. This study investigated the effects of different lengths of food deprivation periods and restricted (fixed-time) feeding on body weight loss as well as anxiety-related and motivated behavior in 5–6 month old male and female Wistar rats. The observed body weight loss was not influenced by sex and ranged between 4% (16 h deprivation) to approximately 9% (fixed-time feeding). Despite significant body weight loss in all groups, the motivation to eat under the aversive test conditions of the modified open field test increased only after 48 h of food deprivation. Long-lasting effects on anxiety as measured in the elevated plus maze test 24 h after refeeding have not been observed, although fixed-time feeding could possibly lead to a lasting anxiogenic effect in female rats. Overall, female rats showed a more anxiolytic profile in both tests when compared to male rats. Despite these sex differences, results suggest that food deprivation is not always paralleled by an increased motivation to feed in a conflict situation. This is an important finding as it highlights the need for tailored pilot experiments to evaluate the impact of food deprivation protocols on animals in regard to the principles of the 3Rs introduced by Russell and Burch.

Central administration of GPR55 receptor agonist and antagonist modulates anxiety‐related behaviors in rats

G-protein-coupled receptor 55 (GPR55) has been proposed as an atypical cannabinoid receptor, which is activated by lysophosphatidylinositols and some synthetic or endogenous cannabinoid molecules. The exact role of GPR55 receptors in the central nervous system especially in anxiety needs to be evaluated. In this study, the effects of intracerebroventricular (i.c.v.) administration of agonist and antagonist of GPR55 receptor on anxiety-related behaviors in rats were investigated. Here, O-1602 (GPR55 agonist) at the doses of 0.2, 1, and 5μg/rat increased %OAT and %OAE but not the locomotor activity, showing an anxiolytic response, whereas i.c.v. injection of ML193 (GPR55 antagonist) at the doses of 0.1 and 1μg/rat increased anxiety-like behaviors while causing locomotor impairment. The antagonistic effect of ML193 on the anxiolytic-like effect of O-1602 was also evaluated. The results showed that ML193 decreased the anxiolytic-like effect of O-1602. Based on these results, it may be concluded that central GPR55 may have a role in modulation of anxiety-like behaviors in rats. Further experiments are needed to elucidate the exact role of these receptors in anxiety.